Pain relieved without numbness
A way of delivering local anaesthetic so that it blocks pain but does
not cause numbness or interfere with motor function has been developed
by researchers at Massachusetts General Hospital and Harvard Medical
School, Boston.
Anaesthetics usually act by diffusing through cell membranes and blocking
sodium channels. But this causes all neurons to be blocked, not just
sensory neurons.
The researchers combined QX-314, a normally inactive derivative of the
local anaesthetic lidocaine, and capsaicin, the pungent ingredient in
chilli peppers, to specifically target pain-sensing neurons.
Capsaicin opens an ion channel called TPRV1, which is only found in pain-sensing
neurons. Unlike most anaesthetics, QX-314 has a permanent positive charge
and cannot infiltrate lipid membranes to block the excitability of the
cell. However, when combined with capsaicin it is able to enter the cell
via the TPRV1 ion channel and shut it down. Other types of neurons are
not affected since QX-314 remains trapped outside.
The researchers injected QX-314 and capsaicin into the hind paws of rats
and found a long-lasting (more than two hours) decrease in their response
to painful thermal and mechanical stimuli. Regional injection near the
sciatic nerve also produced long-lasting decreases in pain sensitivity
without a corresponding motor deficit, say the researchers.
“This strategy for blocking pain should be advantageous for generating
pain-restricted local anaesthesia when preserving motor and autonomic responses
and non-painful sensations is desirable, such as in childbirth and some dental
procedures, as well as treating nociceptor driven chronic pain, such as post-herpetic
neuralgia,” they conclude.
However, the researchers point out that they chose capsaicin and QX-314 for initial
experiments because they are off-the-shelf reagents with well-characterised properties,
but that there may be other reagents better suited to application to humans (Nature 2007;449:607).
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